作为自闭症谱系障碍模型的DSCAM异构性认知行为表型
Ryan C Neff1,2, Katherine A Stangis1, Ujjawal Beniwal1
1Michigan Neuroscience Institute, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Genes, brain, and behavior
|September 18, 2024
概括
唐氏综合征细胞粘附分子 (DSCAM) 功能丧失突变与自闭症谱系障碍 (ASD) 有关. DSCAM异合体小鼠表现出类似ASD的认知和行为缺陷,支持它们作为ASD研究模型的使用.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
- 发展生物学 发展生物学
背景情况:
- 自闭症谱系障碍 (ASD) 影响了美国36个儿童中的1个,患病率不断增加.
- 在DSCAM中发生的新功能丧失 (dnLoF) 突变被确定为显著的ASD风险因素.
- 以前的研究将DSCAM切除与小鼠的社会和行为缺陷联系起来.
研究的目的:
- 在小鼠模型中调查与DSCAM低表达相关的认知和行为现象.
- 为了确定DSCAM哈普洛缺陷是否回顾了与ASD相关的行为全谱.
- 评估DSCAM异合体小鼠对ASD研究的适用性.
主要方法:
- 对DSCAM异合体小鼠 (DSCAM2J+/-) 的综合认知和行为表型.
- 评估多动性,焦虑类行为和运动协调.
- 评估海马体依赖的学习和记忆,包括工作记忆,长期记忆和上下文恐惧学习.
- 隐式学习过程的测试.
主要成果:
- DSCAM异合体小鼠表现出多动,焦虑增加和运动协调缺陷.
- 在海马体依赖性工作记忆,长期记忆和上下文恐惧学习方面观察到显著的损伤.
- 在DSCAM异合体小鼠中,隐式学习过程没有受到影响.
- 观察到的表型与人类ASD病例中观察到的表型非常相似.
结论:
- 在小鼠中失去一个DSCAM副本会导致一系列自闭症类行为,包括认知缺陷.
- 这些发现强化了DSCAM dnLoF突变在ASD病因学中的作用.
- DSCAM异合体小鼠代表了研究ASD和开发潜在干预措施的有价值模型.
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